CN107854519A - A kind of perilla leaf oil and its application - Google Patents
A kind of perilla leaf oil and its application Download PDFInfo
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- CN107854519A CN107854519A CN201710855654.6A CN201710855654A CN107854519A CN 107854519 A CN107854519 A CN 107854519A CN 201710855654 A CN201710855654 A CN 201710855654A CN 107854519 A CN107854519 A CN 107854519A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/535—Perilla (beefsteak plant)
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/11—Aldehydes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
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Abstract
The invention discloses a kind of perilla leaf oil and its application, the content of perillaldehyde is not less than 29% in perilla leaf oil, the perilla leaf oil can be used as active component to be used in herbal mixture to strengthen promoting small bowel peristalsis, antipyretic, anti-inflammatory, antibacterial action, the perilla leaf oil is alternatively arranged as raw material and is used in ageratum series of products, particularly in ageratum dripping pill, also active component can be used as, pharmaceutical preparation is made with pharmaceutically acceptable carrier.
Description
Technical field
The present invention relates to the composition of perilla leaf oil and purposes, the use especially using perillaldehyde as the perilla leaf oil of main component
On the way, field of medicaments is belonged to.
Background technology
Perilla leaf is labiate purple perilla Perilla frutescens (L.) Britt. dried leaf (or with spray),
Record in going through version《Chinese Pharmacopoeia》In, while also record in 15,16 editions《Japanese Pharmacopoeia》In.Going through version《Chinese Pharmacopoeia》In,
To this part of perilla leaf assay, only write exactly and determined according to determination of volatile oil method, keep micro-boiling 2.5 hours, volatile oil content is not
0.40%, the assay item without active ingredient in perilla leaf oil must be less than, in Japanese Pharmacopoeia, specify that in perilla leaf
The content of (dry weight) active ingredient perillaldehyde (Perillaldehyde) must not be less than 0.08%.
The plant resources of purple perilla is widely distributed, and wild resource enriches, while because purple perilla is the integration of drinking and medicinal herbs that the Ministry of Public Health announces
Plant, except hyoscine, flavorant, food pigment and for vegetable consumption are also acted as, consumption figure is big, therefore also shape at home
Into the cultivar of very abundant.From plant classification,《Chinese Plants will》Record purple perilla is autogenus, lower point of 4 changes of kind
Kind, it can substantially be divided according to cultivation with wild, cultivated form has purple perilla P.fruteseens var.frutescens (L.)
Britt. it is in all parts of the country extensive with P.fruteseens var.crispa (Thunb.) two mutation of Hand.-Mazz. of Huis Soviet Union
Cultivation；Agriotype is wild purple perilla P.frutescens var.acuta (Thunb.) Kudo, and ear tooth purple perilla
P.frutescens var.auriculato-dentataC.Y.Wu et Hsuan ex H.W.Li., except northeast and northwest are wide
It is distributed in various regions.
The report that perillaldehyde is extracted on the preparation method of perilla herb oil and from perilla herb oil is as follows：
In " straight-through steaming process extraction Folium Perillae volatile oil process optimization and evaluation " text, Yuan etc. is disclosed using straight
Logical stream mode, is not crushed to perilla leaf, is extracted 3 hours, steam pressure 0.02MPa, and oil-collecting ratio is high, but not
Content is analyzed.(Yuan Xiaoyan etc., steaming process extraction Folium Perillae volatile oil process optimization and evaluation are led directly to,《Chengdu medical science
Institute's journal, 03 phase in 2014)
(200910164797.8 Publication No. CN101613638A) discloses one kind and extracts natural perfume material from green perilla leaf
The clean preparation method of perillaldehyde, this method are to be extracted green perilla leaf using the method for distillation, distillate polymeric adsorbent
Adsorbed, then eluted with ethanol, for eluent using the method recovery ethanol of air-distillation, yellow concentrate is purple
Soviet Union's aldehyde product.
201310670697.0 (Publication No. CN104710294A) disclose the extract method of perillaldehyde, specific steps
For：Raw material squeezes, centrifuge extraction, backflow concentration, absorb-elute, distillation and concentration.
Active ingredient on perilla leaf oil：
In " progress of perilla leaf oil " one text, 5 certain etc. disclose that " also there is part research work report the country, refers both to
The active ingredient for going out perilla leaf oil is mainly perillaldehyde, also a small amount of limonene and australene etc. ", it is " right to it is also proposed certainly
Domestic perilla leaf Chemical Composition of The Essential Oil is analyzed, and as a result finds to be free of perillaldehyde in perilla leaf, and the content of perilla ketone
Very high, common perilla is free of perillaldehyde, and contains perilla ketone ", have different versions.Meanwhile this article is also write exactly, pharmacologically, perilla leaf oil with
Perillaldehyde all has the effect of obvious anti-dermatophyte, and perillaldehyde cooperates with suppression to make the growth of skin filamentous fungi with citral
With.(Wu Yongfu etc., the progress of perilla leaf oil, when treasure's traditional Chinese medical science traditional Chinese medicines, 8 phases of volume 18 in 2007,2019-2020)
The report perillaldehyde such as Yu Zhanyang is the active ingredient in purple perilla, accounts for 50% (this section of content warp of volatilization weight of oil
Often it is cited), but the sample produced according to author to China carries out analysis shows, and purple perilla is simultaneously free of perillaldehyde, and the content of perilla ketone is but
It is higher, and common perilla then contains perillaldehyde, the content of perilla ketone is not then high.(in accounting for ocean etc., the research of purple perilla platymiscium and its newly enter
Exhibition, foreign medical science pharmacy fascicles, 03 phase in 1986)
Also parting will be carried out according to the composition contained in perilla leaf oil by having, and such as be divided into 7 chemical types：1st, PA types, with purple
Aldehyde (content 16-93%) of reviving is main component, sometimes containing micro perilla ketone, has 28 parts to belong to the type；2nd, PK types, with perilla ketone
(content 12-90%) is main component, sometimes containing micro perillaldehyde, has 10 parts to belong to the type；3rd, PAPK types, both containing perillaldehyde
(content 11.5-29.6%) also (content 6.2-30.2%) containing perilla ketone, has 8 parts to belong to the type；4th, PL types, master contain perillene
(content 66.93%), only 1 part of sample belong to the type, belong to rare type；5th, PP types：PP-a types：Main component is apiol
(apiole, 21.75%-81.65%), there are 6 parts to belong to the type；PP-m types, main component are myristicin (73.03%-
83.22%) it is to belong to the type, to have 3 parts；PP-e types:Main component is elemicin (60.06%, 67.38%), has 2 parts to belong to this
Type；PP-as types, main component are asarone (asarone, 23.91%), have 1 part of sample to belong to the type；6th, PT types, mainly into
It is divided into piperitenone (41.73%-46.55%), limonene (26.3%-38.03%), there are 2 parts to belong to the type；7th, F types：Mainly
Composition is 2- hexanoyls furans (2-hexanoylfuran, 39.11%-50.45%), has 2 parts to belong to the type.Therefore, domestic purple perilla
Chemical type (see long tinkling of pieces of jade of Wei etc., the different chemical types of Folium Perillae volatile oil and ground by main chemical type of PA, PK, PAPK, PP type
Study carefully progress, CHINA JOURNAL OF CHINESE MATERIA MEDICA, in August, 2015, the 15th phase of volume 40,2937-2944).
Inventor is studied perilla leaf oil, obtains a kind of new perilla leaf oil and application.
The content of the invention
Extensive in order to solve the above-mentioned perilla leaf oil medicine source referred to, component distributing is complicated, without reliable and secure effective purple perilla
The problem of unified standard of leaf oil, it is an object of the present invention to provide a kind of effective component is clear and definite, safely and effectively purple perilla
Leaf oil.
In the prior art, the content of the perillaldehyde contained in perilla leaf oil is 16-93%, and other compositions are not defined,
The present invention is the selection invention in prior art basis.
The present invention provides a kind of new perilla leaf oil, and the percentage by weight of each component is as follows：
Perillaldehyde 29-70%, carypohyllene 2-27%, perillene or perilla ketone 0-5%, wherein, perillaldehyde and carypohyllene two
Total content of person is 40-85%.
Preferably, new perilla leaf oil of the invention, the percentage by weight of each component are as follows：Perillaldehyde 35-70%, China pink
Alkene 7-27%, perillene or perilla ketone 0-5%, wherein, total content of both perillaldehyde and carypohyllene is 45-85%.
It is further preferred that the new perilla leaf oil of the present invention, the percentage by weight of each component are as follows：Perillaldehyde 40-
62%, carypohyllene 10-27%, perillene or perilla ketone 0-4.1%, wherein, total content of both perillaldehyde and carypohyllene is
56-85%.
Still further preferably, new perilla leaf oil of the invention, the percentage by weight of each component are as follows：Perillaldehyde 40-
55%, carypohyllene 14-22%, perillene or perilla ketone 0-4.1%, wherein, total content of both perillaldehyde and carypohyllene is
60-70%.
Still more preferably, new perilla leaf oil of the invention, the percentage by weight of each component are as follows：Perillaldehyde 40-
53%, carypohyllene 14-22%, perillene or perilla ketone 0-4.1%, wherein, total content of both perillaldehyde and carypohyllene is
60-70%.
Most preferably it is preferably, new perilla leaf oil of the invention that the percentage by weight of each component is as follows：Perillaldehyde 46-
49.2%, carypohyllene 14.5-22%, perillene or perilla ketone 0-4.1%, wherein, the total of both perillaldehyde and carypohyllene contains
Measure as 62-68%.
In above-mentioned perilla leaf oil：
The carypohyllene is β-carypohyllene (β-Caryophyllene), and structure is as follows：
Present invention also offers the preparation method of above-mentioned perilla leaf oil, this method comprises the following steps：
By perilla leaf steam distillation, steam pressure is maintained at 0.1MPa, the timing since oil dripping, distills 3-5 hours,
100-120 DEG C of temperature, distillate is collected after steam condensation, the dregs of a decoction discard, and distillate stands more than 20 minutes, obtains water layer, waves
Hair oil layer and emulsion layer, isolate volatilization oil reservoir, emulsion layer carries out secondary water in addition, the present invention also creatively collects water layer
Steam distillation, distillation time are 30 minutes separation volatilization oil reservoirs, emulsion layer and waved respectively with what first time steam distillation obtained
Hair oil layer, emulsion layer mixing, discard water layer, emulsion layer are stood, and emulsion layer stands more than 12h, merge volatilization oil reservoir and produce purple
Folium perillae oil.
The preferred Hunan Hanshou county of the perilla leaf, Fauna of Taoyuan, Nw Hunan county, Hunan Ding Cheng, Lianyungang of Jiangsu, this is by Chaozhou, Henan
The perilla leaf on the ground such as Nanyang, Guangxi Yulin, Anguo Shi Fo towns, Fuling Chongqing, Shandong Yantai.Unlimited green, one side green one side
The purple perilla of purple or two-sided purple, also unlimited wild purple perilla (P.frutescens var.acuta), be able to can revive
(P.frutescens var.crispa), purple perilla (P.frutescens var.frutescens).
The distillate time of repose is preferably 20-30 minutes.
The emulsion layer time of repose is preferably 12h-18h.
Present invention also offers above-mentioned perilla leaf oil in antibacterial, anti-inflammatory is prepared, promote small bowel peristalsis, antipyretic medicine
Using.The medicine is not limited to perilla herb oil list product, in addition to compound, such as ageratum series of products, is especially applicable to wrinkled giant hyssop
In healthy tendency dripping pill.
A further object of the present invention is to provide a kind of perilla leaf oil preparation, and the perilla leaf oil preparation is with the present invention
Perilla leaf oil is active component, with pharmaceutically acceptable carrier be used together conventional method be prepared into it is pharmaceutically acceptable each
Kind pharmaceutical preparation.
In conjunction with the embodiments and experimental example is further illustrated to the embodiment of the present invention, more clearly to retouch
State advantages of the present invention and feature.But these embodiments are only exemplary, do not form any restrictions to the scope of the present invention.
It will be understood by those skilled in the art that without departing from the spirit and scope of the invention can be to the details and shape of the present invention
Formula is modified or replaced, but these modifications and replacement are each fallen within protection scope of the present invention.
The beneficial effects of the present invention are：
1st, because purple perilla herb resource is extensive, species is various, and component distributing differs greatly, and《Chinese Pharmacopoeia》In again still
The assay item of active ingredient is not included, and perilla leaf oil is often used as medicine directly as raw material, as ageratum series of products, apricot are revived
Granules for treating common cold, wind-solar resources, wind relieving coughing syrup, Jieji ' ningsou piece etc. are dissipated just using perilla leaf oil as prescription element, only wrinkled giant hyssop
Healthy tendency series listing kind just has as many as 650.The difference of perilla leaf oil composition certainly will influence the difference and Difference In Toxicity of drug effect,
There is potent lung selection toxicity to mouse as Wilson B J study report perilla ketone, and before this, everybody is using purple perilla
Perilla leaf only is examined according to the content of total volatile oil in perilla leaf during leaf oil, goes to extract volatile oil with qualified perilla leaf is examined
For prescribed preparation, do not go to pay close attention to the composition in volatile oil, it may occur that potential risks, long-term use will certainly cause body
Body is injured, and therefore, original is traced to the source extremely urgent, inquires into the relation between perilla leaf oil material base and drug effect, and then determine to use
Base and the place of production in the purple perilla medicinal material for preparing perilla leaf oil, and the quality standard of perilla leaf oil is further formulated, for containing purple perilla
The prescribed preparation of leaf oil provides reliable raw material and Research foundation.
2nd, meaning of the present invention is：
(1) preparation method of perilla leaf oil is created, while specify that the pharmacological activity and toxicity of various perilla leaf oils, than
Such as purple perilla ene-type perilla leaf oil, perillaldehyde type perilla leaf oil, perilla ketone type perilla leaf oil, find：Perillaldehyde type perilla leaf oil is imitated
Fruit is good, and toxicity is low, provides for the application of perilla leaf oil in the formulation and clearly instructs.
(2) drug safety and validity of the herbal mixture containing perilla leaf oil are improved.
(3) reliable Research foundation is provided for purple perilla medicinal material and the perfect of perilla leaf oil quality standard.
(4) pharmacology activity research of the perilla leaf oil of different chemical types, direction is specified for deeply developing for perilla leaf oil.
3rd, the present inventor chooses perilla leaf (sample 1, the purple of four parts of different chemical composition types again during project development
Soviet Union's alkene, perilla ketone, perillaldehyde three have；Sample 2：Perillene；Sample 3：Perillaldehyde；Sample 4：Perilla ketone) it is carried out
DNA is extracted and sequence amplification, after sequencing peak figure is pre-processed and spliced, with Chinese medicine DNA bar code identification systems
Alignment is carried out, as a result proves that four parts of perilla leaf samples are certified products purple perilla.As can be seen here, Pharmacognosy Studies are the purple perilla of certified products
Leaf, its internal chemical composition also can be inconsistent.
4th, the preparation method on the present invention：
Steam pressure：If hypertonia, liquid in volatile oil extractor can on gush, the volatile oil extracted can be with
Aqueous go out condenser together and collect less than, cause the wasting of resources, if steam pressure is too low, cause extraction efficiency low,
Extract insufficient, volatilization oil yield is relatively low, and inventor carries out research discovery, and 0.1MPa is that extraction Folium Perillae volatile oil is optimum
Pressure.
Extraction time：It is when observing by the naked eye the liquid level of volatile oil in volatile oil extractor no longer to rise, as to extract
Terminal；
The determination of Extracting temperature is by recording vapor (steam) temperature corresponding to stable extraction pressure, so when extraction pressure stability
When, according to The Ideal-Gas Equation PV=nRT, Extracting temperature is also stable.
The key advantages that the present invention is different from prior art are that the subsequent purification of the volatile oil extracted is handled：Water removal.
Water Yin Qiyi causes drug hydrolysis and easy infection microorganism to frequently result in medicine stability variation, and perilla leaf oil has part water
Dissolubility, so when extracting volatile oil with steam distillation, volatilization oil reservoir can contain partial moisture, while in volatile oil extractor
In very thick emulsion layer occurs, emulsion layer is the mixed layer of volatile oil and water, while because part perilla leaf oil is dissolved in water
Layer and make also to be mixed with part perilla leaf oil in water layer, in order to ensure volatilize oil yield, it is necessary to by the volatile oil and emulsion layer of water layer
In volatile oil separate, the volatile oil of water layer is separated, the mode that the present inventor takes is secondary steam distillation
Mode, technical scheme is：Water layer is collected separately and is placed in steam distillation device, distills 30 minutes, water layer is abandoned
Go, volatilization oil reservoir, emulsion layer respectively with distilling obtained volatilization oil reservoir, emulsion layer merging treatment for the first time.In separate aqueous layer
During the volatile oil of mixing, the present inventor have also been attempted organic solvent extraction in addition to attempting the mode of secondary steam distillation
Mode, but because organic solvent extraction can introduce impurity and dissolvent residual, security risks are brought, and because of perilla leaf oil of the present invention
Volatility, when being mixed with petroleum ether, ethyl acetate organic solvent, the recovery of organic solvent can take away part volatile oil,
Causing the yield of volatile oil reduces.Therefore, consider from the yield and safety perspective of volatile oil, select secondary vapor to steam
The mode evaporated carries out the separation of volatile oil in water layer.The time of secondary steam distillation be also by way of process certification, with
The yield of volatile oil is that index carries out careful investigation, the results showed that, the yield of volatile oil is not further added by after 30 minutes, from carrying
Consider in high yield with production efficiency angle, the time of second distillation is set to 30 minutes.In order to ensure the stabilization of volatile oil
Property must assure that the water in volatilization oil reservoir and emulsion layer is completely separated away, the present inventor once attempted to add different dryings
Agent, the various ways such as means of standing separation go to separate emulsion layer, the results showed that, the means of standing separation both simple possible, again
Other destabilizing factors will not be introduced.By the detailed process certification such as 5,10,15,20,25,30,40 minutes, the results showed that evaporate
Go out liquid and stand more than 20 minutes, the moisture for the oil reservoir that volatilizees can be just completely removed, and emulsion layer passes through 4,8,12,16,20,24 hours
Detailed process checking, the results showed that stand 12h-18h, the yield and stability of isolated perilla leaf oil be best.Therefore,
Consider perilla leaf oil quality and production efficiency, distillate time of repose is set as more than 20 minutes, during the standing of emulsion layer
Between be set as more than 12h, and preferably 12h-18h.
The perilla leaf oil high income prepared using method provided by the invention, water content is few, and purity is high.
5th, by perilla leaf oil provided by the invention compared with existing perilla leaf oil, the present invention is in antibacterial, anti-inflammatory, promotion
Small bowel peristalsis, it is antipyretic above, effect is superior to prior art.
Embodiment
Embodiment 1：The preparation method of perilla leaf oil
1) weigh：10kg perilla leafs are weighed, it is standby；
2) distill：By in perilla leaf the input extractor of cleaned mistake, with steam distillation, steam pressure is maintained at
0.1MPa, the timing since oil dripping, distill 3-5 hours, 100-120 DEG C of temperature；
3) oil is received：Distillate is collected after steam condensation, the dregs of a decoction discard, and distillate stands 20 minutes, obtains water layer, volatile oil
Layer and emulsion layer, isolate volatilization oil reservoir, discard water layer, emulsifying part layer is put into separatory funnel and continues to stand；Emulsion layer
Stand 12h, discard water layer, merge volatilization oil reservoir and produce perilla leaf oil (yield is 0.5%).
Experimental example 1：Content analyte detection
According to the method for embodiment 1, to Hunan Hanshou county, Fauna of Taoyuan, Nw Hunan county, Hunan Ding Cheng, Lianyungang of Jiangsu, this is by tide
The perilla leaf on the ground such as state, Nanyang, henan, Guangxi Yulin, Anguo Shi Fo towns, Fuling Chongqing, Shandong Yantai is handled, extraction system
Standby obtained perilla leaf oil is detected, and specific detection method is：
1st, the preparation of need testing solution：Perilla leaf oil about 0.1g is taken, it is accurately weighed, put in 10ml measuring bottles, add n-hexane dilute
Release to scale, shake up, filter, take subsequent filtrate, produce.
2nd, the preparation of reference substance solution：Take perillaldehyde reference substance appropriate, it is accurately weighed, add n-hexane that every 1ml is made containing purple
Soviet Union aldehyde 4mg solution, is produced.
3rd, GC/MS analysis methods：
Chromatographic condition：Chromatographic column, HP-5MS (30m*250 μm * 0.25 μm), carrier gas are helium, temperature programming, inlet temperature
For 200 DEG C, initial temperature is 50 DEG C, and 10 DEG C/min is raised to 100 DEG C, retains 3min, and 5 DEG C/min is raised to 200 DEG C, retains 3min,
Split ratio：20：1, the μ L of sample introduction 1.
Simple condition, ion gun EI:70eV, 250 DEG C of interface temperature, mass scan range：50-500amu, solvent prolong
Slow time 3min.
4th, analysis result：Folium Perillae volatile oil sample is analyzed using GC/MS methods, entered by database NIST2.0
Row retrieval, checks data of literatures, identifies chemical combination.
Testing result is shown in Table 1-1,1-2,1-3.
Each component content of perilla leaf oil in the how individual samples of table 1-1
| Composition | Molecular formula | Sample 1 | Sample 2 | Sample 3 | Sample 4 | Sample 5 | Sample 6 | Sample 7 | Sample 8 |
| Perillaldehyde | C10H14O | 40.97 | 58.00 | 49.17 | 46.8 | 54.82 | 40.13 | 47.48 | 43.08 |
| Carypohyllene | C15H24 | 20.75 | 27 | 18.79 | 20.04 | 19.00 | 20.69 | 14.66 | 26.27 |
| Perillene | C10H14O | —— | —— | —— | —— | —— | —— | —— | —— |
| Perilla ketone | C10H14O2 | 3.91 | -- | 1.91 | 2.85 | 2.57 | 3.63 | 4.1 | 1.09 |
Each component content of perilla leaf oil in the how individual samples of table 1-2
| Composition | Sample 9 | Sample 10 | Sample 11 | Sample 12 | Sample 13 | Sample 14 | Sample 15 | Sample 16 |
| Perillaldehyde | 41.96 | 70.00 | 49.03 | 61.24 | 53.00 | 39.50 | 54.00 | 51.86 |
| Carypohyllene | 14.12 | 3.15 | 16.17 | 14.73 | 16.82 | 10.15 | 2.31 | 8.77 |
| Perillene | —— | —— | —— | —— | —— | —— | —— | —— |
| Perilla ketone | 0.91 | —— | 1.91 | 2.85 | 0.91 | —— | 1.23 | 1.54 |
Each component content of perilla leaf oil in the how individual samples of table 1-3
| Composition | Sample 17 | Sample 18 | Sample 19 | Sample 20 | Sample 21 | Sample 22 | Sample 23 |
| Perillaldehyde | 35.00 | 47.02 | 29.53 | 32.64 | 50.00 | 46.00 | 35.00 |
| Carypohyllene | 10.92 | 7.65 | 27.00 | 8.99 | 5.72 | 8.77 | 12.99 |
| Perillene | —— | —— | —— | —— | —— | —— | —— |
| Perilla ketone | 1.93 | 0.86 | 0.24 | 0.25 | 0.57 | 0.63 | 1.31 |
Note：-- not detect
Experimental example 2：The detection of moisture
1st, detection method is Ka Erfeixiushi non-aqueous titrations, and mensuration program is as follows：
(1) demarcate：Demarcated, be repeated three times with weight reduction with 20 microlitres of purified waters, demarcation content three times
When RSD is not more than 1.0%, sample measure can be carried out.
(2) sample determines：Weigh 0.1g samples to be measured, every part of sample is repeated three times, and content RSD three times is not
During more than 1.0%, the moisture (%) of the average, as sample of measured value three times is recorded.
2nd, testing result：It is shown in Table 2-1,2-2,2-3
Table 2-1：Influence of the secondary steam distillation time to total volatile oil yield
Explanation：1st, weight × 100% of weight/extraction perilla leaf of volatilization oil yield=volatile oil
2nd, the volatilization oil yield at 0 moment is the volatilization oil yield that first time steam distillation obtains.
Table 2-2：Influence of the distillate time of repose to moisture
Table 2-3：Influence of the emulsion layer time of repose to moisture
——：Expression does not detect.
Table 2-1 results are shown：The secondary steam distillation time, the volatile oil in water layer could be complete more than 30 minutes
Separate, more than 30 minutes, the yield of volatile oil is not further added by, and therefore, is considered from improving yield and improving efficiency, will be secondary
The time of steam distillation is preferably 30 minutes.
Table 2-2 results are shown：Distillate stands more than 20 minutes, and the moisture for the oil reservoir that volatilizees can be just completely removed, preferably
Time is 20-30 minutes.
Table 2-3 results are shown：When emulsion layer time of repose is less than 12h, the moisture value of gained perilla leaf oil is higher than 3%, shadow
Ring the stability of perilla leaf oil；When emulsion layer time of repose is more than 18h, the moisture value of gained perilla leaf oil no longer reduces, for
Save the time and improve efficiency consideration, be preferably 12h-18h by emulsion layer time of repose.
The preparation of the ageratum dripping pill of embodiment 2
1st, prescription：Rhizoma atractylodis 160g, dried orange peel 160g, stir-baked CORTEX MAGNOLIAE OFFICINALIS with rhizoma zingiberis recens juice 160g, root of Dahurain angelica 240g, Poria cocos 240g, shell of areca nut 240g, raw half
Summer 160g, extract of licorice root 20g, patchouli oil 1.6ml, perilla leaf oil 0.8ml (purple perilla aldehyde about 47.02%, the table of experimental example 1
1-3 sample 17).
2nd, preparation method：
(1) ten taste more than, rhizoma atractylodis, dried orange peel, the root of Dahurain angelica, stir-baked CORTEX MAGNOLIAE OFFICINALIS with rhizoma zingiberis recens juice add the extraction of 70% alcohol reflux secondary, 2 hours for the first time,
Second 1 hour, filtration, decompression filtrate recycling ethanol, it was 1.15 (75 DEG C) to be concentrated into relative density, standby；Poria cocos, the shell of areca nut
Add water to cook secondary, 2 hours first times, second 1 hour, decocting liquid filtration, filtrate decompression is concentrated into relative density as 1.05 (75
DEG C), add extract of licorice root, mixing for standby use；Dried pinellia is soaked, and changes water for every eight hours once, is steeped to the saturating heart, separately adds rhizoma zingiberis
13.5g, add water to cook secondary, 3 hours first times, second 2 hours, decocting liquid filtration, filtrate is concentrated into relative density as 1.04
(75 DEG C), adding ethanol makes alcohol content stand up to 60%, take supernatant, reclaim ethanol, decoction merges with above-mentioned concentrate, dense
It is reduced to the thick paste that relative density is 1.32.
(2) Macrogol 6000 765g is weighed, 85 DEG C of heating make melting, add patchouli oil, purple prepared by embodiment 1
Folium perillae oil and above-mentioned thick paste, mix, dripping pelletization, film coating, about 1066g is made, produces.
The apricot of embodiment 3 Soviet Union granules for treating common cold
1st, prescription：Semen armeniacae amarae 63g, dried orange peel 47g, perilla leaf oil 3.1ml (purple perilla aldehyde about 46%, the table 1-3 of experimental example 1
Sample 22), root of purple-flowered peucedanum 63g, balloonflower root 47g, radix glycyrrhizae 16g.
2nd, preparation method：Semen armeniacae amarae is taken to smash to pieces, warm water is soaked 24 hours, steam distillation, collects distillate 50ml extremely
In 90% ethanol 0.8ml, then redistillation is once, collects re-distilled liquid cause, determines re-distilled liquid hydrogen cyanide content, is diluted with water
It is standby to every 1ml 3.0mg containing hydrogen cyanide semen armeniacae amarae re-distilled liquid；The root of purple-flowered peucedanum, dried orange peel extraction volatile oil, the dregs of a decoction and balloonflower root, radix glycyrrhizae
Add water to cook secondary, 2 hours every time, collecting decoction, filtration, filtrate was concentrated into right amount, and it is appropriate to add sucrose, and particle is made, dry
It is dry to let cool, above-mentioned semen armeniacae amarae re-distilled liquid 17ml and perilla leaf oil, dried orange peel, root of purple-flowered peucedanum volatile oil are sprayed into, mixes, 1000g is made, i.e.,
.
Embodiment 4：Perilla leaf oil soft capsule
1st, weigh：Weigh perilla leaf oil 1Kg (purple perilla aldehyde about 54.00%, the table 1-2 of experimental example 1 sample 15), one-level
Finished product rapeseed oil 1kg, gelatin 150LB8 2kg, glycerine 0.6kg, purified water：3.3kg, it is standby；
2nd, glue is changed：By in the glycerine of recipe quantity, purified water being placed in glue tank, it is well mixed, is heated to 80 DEG C, opens
Stirring, equably put into gelatin, be warming up to glue temperature and be maintained at 80-90 DEG C, to transparent glue solution without micelle when close stirring, it is quiet
Put 1 hour；
3rd, material：The perilla leaf oil of recipe quantity and rapeseed oil are placed in material tank, stirred, closed standing；
4th, dripping：By in glue and decoction input soft capsule dripping equipment, condensate temperature is kept in 8-18 DEG C of unit,
Glue temperature starts dripping in the range of 65-75 DEG C in glue groove；
5th, shape, dry：Capsule and pill is placed in and rolled in rotating cage, sizing is blowed.Appropriate block side is put into every time in per cage
Towel wipes capsule and pill surface, when check the clean conditions on shawl surface and change in time, the capsule and pill after sizing is placed in drying box
It is dried, the temperature of dry wind is no more than 34 DEG C, and relative humidity is no more than 35%, dries to film moisture<10% produces purple
Perilla leaf fat capsule.
Embodiment 5：Perilla leaf oil capsule
1st, prepared by perilla leaf oil Benexate Hydrochloride：1kg beta-schardinger dextrins are weighed, are placed in container, add appropriate distillation
Water, heating water bath dissolve beta-schardinger dextrin, prepare the inclusion aqueous solution of beta-schardinger dextrin, then slowly instill Folium Perillae volatile oil
100ml (is dissolved in 1 times of ethanol of volume 95%), after being included 4 hours with 75rpm speed stirring at the corresponding temperature, to refrigerator
Middle refrigeration 24 hours, filters, washs inclusion compound with suitable quantity of water, ether respectively and be precipitated to non-volatile oil gas taste, and it is small to dry 6 in 40 DEG C
When, produce inclusion compound；
2nd, capsule is filled：1) after inclusion compound is well mixed with appropriate talcum powder, capsule is poured into, produces perilla leaf oil capsule.
Experimental example 3：The antipyretic experiment of the perilla leaf oil of different chemical types, promote small intestine push experiment, anti-inflammatory experiment
First, materials and methods
1st, by test product：Extractive of perilla, China Medical Sciences Academy Medical Plants Institute's identification research room provide lot number：
20151206。
PL water extracts：Every 100 grams of crude drugs obtain 20.03g water extracts (PL is perillene)；
PA water extracts：Every 100 grams of crude drugs obtain 16.53g water extracts (PA is perillaldehyde)；
PK water extracts：Every 100 grams of crude drugs obtain 22.52g water extracts (PK is perilla ketone)；
PL oil：Every 100 grams of crude drugs obtain 0.361g extracts, wherein PL contents are 71.21% after testing.
PA oil：Every 100 grams of crude drugs obtain 0.312g extracts, wherein PA contents are 74.32% after testing.
PK oil：Every 100 grams of crude drugs obtain 0.609g extracts, wherein PK contents are 76.18% after testing.
2nd, experimental animal：SD rats, non-inbred strais closed colony, male.Body weight：180-200g, 190；ICR mouse, it is non-
Inbred strais closed colony, body weight：18-20g, 216.There is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., the quality certification
Number:SCXK (capital) 2012-0001.
3rd, tester：
METTLER TOLEDO AL104 Mettler-Toledo Instrument (Shanghai) Co., Ltd.；
Manual punch Dezhou Run Xin laboratory apparatus Co., Ltd produces.
4th, medicine and reagent：Dimethylbenzene (500ml) analyzes pure Beijing Changhai chemical plant, lot number：141204
Antipyretic analgesics：Jiamusi pharmaceutical factory produces, specification:0.423g/ pieces, lot number:120809.
Prednisone piece:Zhejiang Province XianJu Pharmacy stock Co., Ltd, lot number：150115
MAREN RUNCHANG WAN:Beijing TongrenTang Co., Ltd Tongrentang Pharmaceutical Factory produces, Chinese medicines quasi-word Z11020159,
Lot number:15015655, specification:6 grams are weighed per ball.
5th, dose design：States Pharmacopoeia specifications purple perilla crude drug dosage be 5-10g crude drugs/person/day, convert and be for rat equivalent
1.025g crude drug/kg.
Test first：2 multiple doses of experimental measuring behaviour equivalent, i.e. 2.05g crude drugs/kg, convert extract dosage
Tested.
Secondary experiment：The equivalent of experimental measuring behaviour dosage, i.e. 1.025g crude drugs/kg, conversion extract dosage are carried out
Experiment.
6th, test method:
1) to the effect of rat fever model caused by yeast：From body weight 180-200g rats, normal body temperature (one is first measured
As be 36.6~38.3 DEG C, 6cm or so in anus thermometre insertion anus).From body temperature eligible, in the yeast of dorsal sc injection 10%
Suspension 5ml/Kg, aobvious author (more than the 0.8 DEG C) rat of selection heating, is randomly divided into 10 groups, gives respectively after body temperature rising
Treat reagent, comparison medicine etc., 1 after administration, 2,3,4h survey body temperature once, record Temperature changing, to observe the effect of bupleurum extract.
2) inhibitory action of paraxylene induced mice ear swelling：Every group of 15 mouse, male and female half and half, gastric infusion are right
Give distilled water gavage according to group, positive controls select prednisone, and each group smears 20ul dimethylbenzene in the right side per mouse 1h after gavage
Ear, put to death after 1h, cut every mouse bilateral external ear, take skin in the middle part of every mouse external ear to weigh with 8mm card punch, calculate left and right ear weight
Difference, calculate the inhibiting rate to swelling.{ (auris dextra weight-left ear weight)/left ear weight } represents as swelling rate (%), compares administration group
With the difference of control group swelling rate.
3) to the effect of mouse small intestine motion：Mouse 96 similar in taking 20 hours body weight of fasting, is randomly divided into 8 groups, often
Group 12, picric acid mark.Each group gavages the drug suspension 0.2ml/10g body weight containing 50% carbonic ink respectively.After administration
30min takes off cervical vertebra and put to death, and opens abdominal cavity separation mesenterium, clip upper end to pylorus, the intestinal tube of lower end to ileocecus, is placed in pallet
On.Small intestine is gently pulled into straight line, measurement Length of intestine is used as " total small intestinal length ".From pylorus to the distance conduct in prepared Chinese ink forward position
" prepared Chinese ink in the intestine advance distance ", prepared Chinese ink ink propulsive rate is calculated with formula.Every group takes average to be compared.
Method of administration and volume：Oral administration gavage, rat, 1ml/100g, mouse 0.2ml/10g, control group are given in equal volume
Distilled water.
Statistical method：All data are handled using SPSS13.0 statistical softwares, are compared between group and are examined using t, measurement data
WithRepresent.
2nd, result
1st, influence of the extractive of perilla to rat temperature increased value of being generated heat caused by yeast：It is shown in Table 3-1
Table 3-1 extractive of perilla to caused by yeast generate heat rat temperature increased value influence (N=10)
aa：Compared with control group, P<0.01
b：Compared with model group, P<0.05；Bb, compared with model group, P<0.01
From result above, compared with control rats, model group rats body temperature is significantly raised after modeling 5h, there is system
Meter learns difference (P ＜ 0.01).Compared with model group, positive controls antipyretic analgesics can obviously reduce the rat caused by dry ferment
Body temperature raises, and 1h works after administration, and sustainable 4 hours cool, hints model success.Compared with model group, purple perilla extraction
Thing volatile oil part and PK water extractions part play the role of to reduce heating rat temperature, have started within 1 hour after volatile oil local administration
There are significant difference (P at effect, four time points of PA types<0.01), 1-2 hours variant (P after the administration of PK types<0.05), 3-4 is small
When have pole significant difference (P<0.01) comparing refrigeration function between, volatile oil is various does not have significant difference.After the administration of PL types
1-3 hours statistically significant (P<0.05), the statistically significant (P of 3-4 hour refrigeration functions after PK water extractions local administration<
0.05), PA and PL water extractions part is not presented with refrigeration function.
2nd, influence of the extractive of perilla to rat temperature increased value of being generated heat caused by yeast：It is shown in Table 3-2
Table 3-2 extractive of perilla to caused by yeast generate heat rat temperature increased value influence (N=10)
Compared with control group, aaP<0.01
Compared with model group, bP<0.05, bb P<0.01
From result above, compared with control rats, model group rats body temperature is significantly raised after modeling 5h, there is system
Meter learns difference (P ＜ 0.01).Compared with model group, positive controls antipyretic analgesics can obviously reduce the rat caused by dry ferment
Body temperature raises, and 1h works after administration, and sustainable 4 hours cool, hints model success.Reducing each experimental group dosage
Afterwards, extractive of perilla PK volatile oil part plays the role of to reduce heating rat temperature, and 2 hours after administration start to work, with model
Group compares, variant (P ＜ 0.05) in 2h, 3h point, has significant difference (P ＜ 0.01) in 4h points, effect lasts and stablize, PA
2h points have significant difference (P ＜ 0.01) to volatile oil upon administration, but are significantly rebounded in subsequent period body temperature, in rising
Trend.Water extraction each several part does not show obvious refrigeration function under test dose.
As a result prompt：The chemical composition that the refrigeration function of extractive of perilla is different from forms and the close phase of test dose
Close.
3rd, the inhibitory action of extractive of perilla paraxylene induced mice ear swelling：It is shown in Table 3-3
Table 3-3：Extractive of perilla paraxylene induced mice ear swelling inhibitory action (N=15)
| Packet | Dosage | Control is picked up the ears (mg) | Inflammation is caused to pick up the ears (mg) | Swelling percentage (%) |
| Control group | --- | 45.96±2.85 | 87.56±9.15 | 90.95±21.06 |
| Prednisone | 25mg/kg | 44.07±3.02 | 64.73±9.07 | 47.36±21.85aa |
| PL water extracts | 0.8212g/kg | 42.51±2.97 | 81.81±11.70 | 92.34±24.00 |
| PL oil | 0.36mg/kg | 42.84±3.31 | 79.74±17.33 | 86.33±38.46 |
| PA water extracts | 0.6778g/kg | 42.45±4.72 | 75.07±9.85 | 77.67±21.88 |
| PA oil | 12.792mg/kg | 43.29±3.49 | 74.51±9.55 | 73.71±28.93 |
| PK water extracts | 0.9234g/kg | 43.62±3.58 | 78.29±10.75 | 80.57±27.40 |
| PK oil | 24.96mg/kg | 42.84±5.96 | 75.36±12.65 | 76.74±24.78 |
aa：With control group than P ＜ 0.01
Prompted by result above, the various volatile oil of purple perilla and water extract have no obvious and suppress mouse dimethylbenzene induced mice ear
The effect of swelling.
4th, the effect that extractive of perilla promotes to mouse small intestine：It is shown in Table 3-4
Table 3-4：Effect that extractive of perilla promotes to mouse small intestine (N=12)
| Packet | Dosage | Small intestine total length (cm) | Promote length (cm) | Swelling percentage (%) |
| Control group | --- | 43.23±6.38 | 17.03±6.23 | 39.95±14.49 |
| MAREN RUNCHANG WAN | 5.6g/kg | 42.12±7.21 | 26.17±7.38 | 63.99±18.97aa |
| PL (water) | 0.8212g/kg | 42.25±4.78 | 18.96±6.67 | 44.61±13.14 |
| PL (oil) | 0.36mg/kg | 42.13±5.42 | 19.04±4.76 | 45.09±9.53 |
| PA (water) | 0.6778g/kg | 42.63±5.68 | 18.75±5.10 | 44.56±13.26 |
| PA (oil) | 12.792mg/kg | 43.33±5.15 | 21.17±5.65 | 49.15±12.75 |
| PK (water) | 0.9234g/kg | 43.42±4.78 | 20.42±5.21 | 47.38±12.94 |
| PK (oil) | 24.96mg/kg | 42.88±6.04 | 26.71±7.95 | 63.72±21.33aa |
aa：With control group than P ＜ 0.01
Experimental result is prompted：In the various water extract of purple perilla and extractive of volatile oil, only PK volatile oil is small with being obviously promoted
The effect of Intestinal pushing, relatively there is pole significant difference (P with control group<0.01), there is statistical significance.
In people with the multiple dose of equivalent 2, purple perilla volatile oil PA, PK, PL type and purple perilla water extract PK types are to caused by yeast
Rat fever model has certain refrigeration function, by being seen on the onset time and duration of refrigeration function, action intensity according to
Secondary is PA (oil)>PK (oil)>PL (oil)>PK (water), but the various no significant difference of effect；In people's dosage dose,equivalent
Under, purple perilla volatile oil PA, PK type has certain refrigeration function to rat fever model caused by yeast, and remaining each several part does not show
Go out obvious refrigeration function.
3rd, conclusion
It is antipyretic：In people with the multiple dose of equivalent 2, purple perilla volatile oil PA, PK, PL type and purple perilla water extract PK types are to yeast
Caused rat fever model has certain refrigeration function, and by being seen on the onset time and duration of refrigeration function, effect is strong
Degree is followed successively by PA (oil)>PK (oil)>PL (oil)>PK (water), but the various no significant difference of effect；It is equivalent in people's dosage
Under dosage, purple perilla volatile oil PA, PK type has certain refrigeration function to rat fever model caused by yeast, and remaining each several part is not
Show obvious refrigeration function.
Promote small intestine push：Purple perilla volatile oil PK types have the function that to promote mouse small intestine to promote.
Anti-inflammatory：Purple perilla volatile oil and the various paraxylene induced mice ear swelling of water extract do not show obvious suppression and made
With.
To sum up, in terms of antipyretic, anti-inflammatory, promotion small intestine push, the perilla leaf oil of purple perilla ene-type is invalid, perilla ketone type
Perilla leaf oil effect is best, and the perilla leaf oil effect of perillaldehyde type is taken second place, but according to the literature, the perilla leaf oil of ketone type is poisonous
Property, inventor has carried out the toxicologic study experiment of aldehyde type and ketone type again.
Experimental example 4：The studies on acute toxicity of perillaldehyde type perilla leaf oil and perilla ketone type perilla leaf oil is tested
1st, experimental animal：ICR mouse, SPF levels, male and female half and half, body weight 18-22g, tonneau China experimental animal is tieed up purchased from Beijing
Technology Co., Ltd..
2nd, laboratory sample：
Perillaldehyde type perilla leaf oil：Purple perilla aldehyde is 47%, lot number：20141025；
Perilla ketone type perilla leaf oil：The content of perilla ketone is 44%, and purple perilla aldehyde is 2.8%, and perillene content is
1.1%, lot number：20140901.
3rd, medication：Single gives tested material in one day, to reach design dosage.
Experiment packet and dosage setting：Set according to the physicochemical property of perillaldehyde in perilla leaf oil and component content combination document
Determine preliminary experiment dosage, the dead minimum dose (Dn) of each tested material 0 and 100% dead maximum agent are found out by trial test
Measure the estimate of (Dm).Experiment is using tested material stoste as predose, according to 18.32g/kg (1/2 stoste) 7.328g/kg (1/5
Stoste), 3.664g/kg (1/10 stoste), 1.832g/kg (1/20 stoste), 732.8mg/kg (1/50 stoste), 366.4mg/kg
(1/100 stoste) carries out gradient dilution to each tested material, and each dosage chooses 2 animals (female half and half), according to dead in 24h
Situation, to determine LD50Possible range：Perilla leaf oil B Dn are 732.8mg/kg (1/50 stoste), and Dm is 3.664g/kg (1/10
Stoste).
According to preliminary result, sample acute toxicity LD50Between 0.733~3.664g/kg, if maximum dosage
For 5.64g/kg, if group spacing i=0.65, drug dose group sets 6 groups altogether, respectively 5.64,3.66,2.38,1.55,1.01 and
0.65g/kg.Take each 5 of male and female mouse, every group of 10 animals.Observed after giving tested material by tested material administration way.
Equally, preliminary experiment is set to medicament according to the physicochemical property of perilla ketone in perilla leaf oil and component content combination document
Amount, the estimation of the dead minimum dose (Dn) of each tested material 0 and 100% dead maximum dose (Dm) is found out by trial test
Value.Experiment is using tested material stoste as predose, according to 7.72g/kg (1/5 stoste), 3.86g/kg (1/10 stoste), 1.93g/
Kg (1/20 stoste), 772mg/kg (1/50 stoste), 386mg/kg (1/100 stoste), 193mg/kg (1/200 stoste),
77.2mg/kg (1/500 stoste), 38.6mg/kg (1/1000 stoste), 19.3mg/kg (1/2000 stoste) enter to each tested material
Row gradient dilution, each dosage chooses 2 animals (female half and half), according to death condition in 24h, to determine LD50Possible range：
Perilla leaf oil A Dn are 38.6mg/kg (1/1000 stoste), and Dm is 77.2mg/kg (1/500 stoste).
According to preliminary result, sample acute toxicity LD50Between 38.6~77.2mg/kg, if maximum dosage
For 114.37mg/kg, if group spacing i=0.75, drug dose group sets 6 groups altogether, respectively 114.37,85.78,64.33,
48.25th, 36.19 and 27.14mg/kg.Take each 5 of male and female mouse, every group of 10 animals.Given by tested material administration way tested
Observed after thing.
Its basic operation formula is：lgLD50(the x of=∑ 1/2i+xi+1)(pi+1-pi)
Wherein, XiFor dosage logarithm, piFor the death rate.
LD5095% fiducial limit=lg-1 (lgLD50±1.96×S m)
Wherein,
S m：Standard error；d：Logarithmic difference；n：Experimental animal number
4th, experimental result：
4.1 perillaldehyde type perilla leaf oil acute toxicity testing animal dead distribution situations are shown in Table 4-1.
Table 4-1 perillaldehyde type perilla leaf oil acute toxicity test animal dead distribution situations
Table 4-1 results are shown：Orally administration perillaldehyde type perilla leaf oil, mouse occurs autonomous after 5.64g/kg groups 15min
Activity is reduced, and with reposing, ataxia occur in most mouse after 20min, or even has the symptoms such as mandatory twitch, 2 hours
After start to occur dead, the administration same day, 10 mouse were all dead.Mouse occurs certainly after 10min after the administration of 3.66g/kg dosage groups
Main activity is reduced, and the symptom such as repose, wherein 1 symptom that has a convulsion, starts dead successively, the same day 10 after administration after 3 hours
Mouse is all dead.There is autonomic activities reduction in mouse after 2.38g/kg dosage groups administration 20min, and the symptom such as reposed, and administration is worked as
Day 4 dead mouses, first day 4 dead mouse after administration.Mouse reposes after 1.55g/kg dosage groups administration about 15min
Deng abnormal response, but it is dead without occurring.Also there is autonomic activities and the abnormal symptom such as reduce, repose in 1.01g/kg dosage groups；
0.65g/kg dosage groups 1 only occur outside autonomic activities reduction, show no obvious abnormalities symptom.Surviving animals continue to observe, and feed disappears
Consumption is normal, and body weight grows steadily, and outward appearance, behavior, secretion, excreta are showed no obvious abnormalities.Calculated according to karber's method
To LD50For 2090mg/kg, 95% fiducial limit：2360mg/kg~1860mg/kg.
4.2 perilla ketone type perilla leaf oil acute toxicity testing animal dead distribution situations are shown in Table 4-2
Table 4-2 perilla ketone type perilla leaf oil acute toxicity test animal dead distribution situations
Table 4-2 results are shown：Orally administration perilla ketone type perilla leaf oil, mouse shows after 114.37mg/kg groups 14min
Sweat, excitement, hair is combed, occur the symptoms such as close mesh, autonomic activities is reduced after 25min, 7 dead mouses of the same day, administration is administered
First day 3 dead mouse afterwards.After the administration of 85.78mg/kg dosage groups 40min mouse occur perspiration, the symptom such as excitement and with
Comb hair, 3 dead mouses of the same day after administration, first day 3 dead mouse after administration, second day 2 dead mouse.
There is autonomic activities reduction in mouse after the administration of 64.33mg/kg dosage groups, combs hair and has the symptoms such as perspiration, the same day 2 is administered
Dead mouse, first day 2 dead mouse after administration.Mouse has perspiration after the administration of 48.25mg/kg dosage groups, combs hair etc.
Abnormal response, but it is dead without occurring.There is autonomic activities and reduce, perspire, comb in 36.19 and 27.14mg/kg, two dosage groups
Manage the abnormal symptoms such as hair；Surviving animals continue to observe, and feed consumption is normal, and body weight grows steadily, outward appearance, behavior, secretion
Thing, excreta are showed no obvious abnormalities.LD is calculated according to karber's method50For 70.13mg/kg, 95% fiducial limit：24.249g/
Kg~19.059g/kg.
5th, experimental summary：It can be seen from experiment above：Purple perilla ene-type perilla leaf oil effect is poor, perilla ketone type perilla leaf
Although oil is also effective, toxicity is larger, the toxicity of perilla ketone type perilla leaf oil be 29 times of perillaldehyde type perilla leaf oil it
It is more, therefore, in pharmaceutical preparation afterwards, perilla leaf oil is used if desired, must strictly detect wherein chemical composition, with
Exempt from that toxic reaction occurs.
Experimental example 5：The further Probe into effect of perillaldehyde type perilla leaf oil
Perillaldehyde type perilla leaf oil is further explored inventor, and experimental method is as follows：
Experimental method is the same as experimental example 3.
It is grouped into：Experimental group 1-9, contrast groups 1-3, wherein experimental group 1 are sample 20 (perillaldehyde and the stone in experimental example 1
Bamboo alkene total content for 41.63%), experimental group 2 be that (perillaldehyde and carypohyllene total content are for sample 17 in experimental example 1
45.92%), experimental group 3 be sample 9 (perillaldehyde and carypohyllene total content be 56.08%) in experimental example 1, experimental group 4 be for
Sample 16 (perillaldehyde and carypohyllene total content be 60.63%) in experimental example 1, experimental group 5 are that the sample 7 in experimental example 1 is (purple
Soviet Union's aldehyde and carypohyllene total content for 62.14%), experimental group 6 be sample 11 (perillaldehyde and carypohyllene total content in experimental example 1
For 65.30%), experimental group 7 be sample 3 (perillaldehyde and carypohyllene total content be 67.96%) in experimental example 1, experimental group 8 be
Sample 13 (perillaldehyde and carypohyllene total content be 69.82%) in experimental example 1, experimental group 9 are that the sample 9 in experimental example 1 is (purple
85%) Soviet Union's aldehyde and carypohyllene total content is.Control group is the sample not within the scope of the present invention during random detection.
Experimental result：
1st, influence of the perillaldehyde type perilla leaf oil of heterogeneity content to yeast heating rat temperature increased value：It is shown in Table 5-
1
Table 5-1：The perillaldehyde type perilla leaf oil of heterogeneity content to yeast generate heat rat temperature increased value influence (N=10)
Note：Aa is the P compared with control group<0.01；
B is the P compared with model group<0.05；Bb is the P compared with model group<0.01；
C is the p compared with contrast groups<0.05, cc is the P compared with contrast groups<0.01.
From table 5-1 results, compared with control rats, model group rats body temperature is significantly raised after modeling 5h, has
Significant difference (p<0.01).Compared with model group, positive controls antipyretic analgesics can obviously reduce big caused by dry ferment
Mouse body temperature raises, and 1h works after administration, and sustainable 4 hours cool, hints model success.Compared with model group, each experiment
The antipyretic response of group is significantly better than that model group, and three contrast groups do not have remarkable result then；Compared with contrast groups, each experimental group has
Different degrees of antipyretic response difference.
Test result indicates that：When content summation is antipyretic to its for perillaldehyde, both carypohyllenes component content in perilla leaf oil
Pharmacological activity influences notable, and when perillaldehyde component content is in 46-49.2%, carypohyllene component content is in 14.5-22%, purple perilla
Alkene or perilla ketone 0-4.1%, wherein, when total content of both perillaldehyde and carypohyllene is 62-68%, antipyretic response is most aobvious
Write, 1-4 hours energy continued down, and have significant difference (p four time points upon administration<0.01).
2nd, the inhibitory action of the perillaldehyde type perilla leaf oil paraxylene induced mice ear swelling of heterogeneity content：It is shown in Table
5-2
The perillaldehyde type perilla leaf oil paraxylene induced mice ear swelling of table 5-3 heterogeneity contents inhibitory action (N=15)
| Packet | Dosage | Control is picked up the ears (mg) | Inflammation is caused to pick up the ears (mg) | Swelling percentage (%) |
| Control group | --- | 44.14±1.85 | 88.04±10.03 | 91.03±22.18 |
| Prednisone | 25mg/kg | 43.07±2.05 | 65.02±11.28 | 47.36±21.85aa |
| Experimental group 1 | 12.792mg/kg | 44.10±2.03 | 67.21±10.29 | 50.14±23.29a |
| Experimental group 2 | 12.792mg/kg | 42.99±3.92 | 68.10±11.09 | 51.36±20.98a |
| Experimental group 3 | 12.792mg/kg | 43.82±2.77 | 69.83±10.24 | 52.23±23.03ac |
| Experimental group 4 | 12.792mg/kg | 44.05±2.92 | 68.54±9.07 | 51.09±22.14ac |
| Experimental group 5 | 12.792mg/kg | 42.98±3.13 | 65.52±9.29 | 48.38±20.55aacc |
| Experimental group 6 | 12.792mg/kg | 43.44±2.81 | 64.69±10.12 | 49.39±22.18aacc |
| Experimental group 7 | 12.792mg/kg | 42.99±2.56 | 65.08±9.98 | 48.24±21.45aacc |
| Experimental group 8 | 12.792mg/kg | 43.87±3.14 | 67.13±11.14 | 50.92±20.14ac |
| Experimental group 9 | 12.792mg/kg | 44.11±2.11 | 68.09±10.23 | 51.29±24.05ac |
| Contrast groups 1 | 12.792mg/kg | 43.59±2.01 | 78.27±9.54 | 73.75±29.13 |
| Contrast groups 2 | 12.792mg/kg | 42.97±2.94 | 78.59±10.73 | 74.27±25.41 |
| Contrast groups 3 | 12.792mg/kg | 44.01±2.52 | 77.39±11.64 | 73.77±22.98 |
Note：A is the P compared with model group<0.05；Aa is the P compared with model group<0.01；C is the p compared with contrast groups<
0.05, cc is the P compared with contrast groups<0.01.
From table 5-2 results, the present inventor is made it was unexpected that different from experimental example 3, caused by each experimental group paraxylene
Mice ear show different inhibitory action, compared with experimental group, each contrast groups, which are showed no, obvious suppresses mouse two
Toluene induced mice ear swelling acts on.
Knowable to the component difference of the perilla leaf oil of Comprehensive Experiment example 3 and each contrast groups, perillaldehyde, carypohyllene in perilla leaf oil
The two component content and content sum are notable to its anti-inflammatory pharmacology activity influence, and when perillaldehyde component content is in 46-49.2%,
Carypohyllene component content in 14.5-22%, perillene or perilla ketone 0-4.1%, wherein, both perillaldehyde and carypohyllene it is total
When content is 62-68%, Inflammatory effects caused by paraxylene are most notable, there is pole significant difference (p compared with contrast groups<
0.01)。
3rd, the effect that the perillaldehyde type perilla leaf oil of heterogeneity content promotes to mouse small intestine：It is shown in Table 5-3
The effect that the perillaldehyde type perilla leaf oil of table 5-3 heterogeneity contents promotes to mouse small intestine（N=12)
Note：A is the P compared with model group<0.05；Aa is the P compared with model group<0.01；C is the p compared with contrast groups<
0.05, cc is the P compared with contrast groups<0.01.
From table 5-3 results, equally the present inventor is made it was unexpected that different from experimental example 3, each experimental group is respectively provided with bright
The aobvious effect for promoting small intestine push, is observed, each contrast groups are consistent with the result of experimental example 3, are showed no with reference to each contrast groups result
It is obvious to promote Constipation, it follows that perillaldehyde type perilla leaf oil can also promote small intestine push, simply small intestine is pushed away
The facilitation effect entered is relevant with perillaldehyde in perilla leaf oil and the content of carypohyllene and the two content sum, when perillaldehyde composition contains
Amount in 29-70%, carypohyllene component content in 2-27%, perillene or perilla ketone 0-4.1%, wherein, perillaldehyde and carypohyllene
When the total content of the two is in the range of 40-85%, perillaldehyde type perilla leaf oil can just show to promote Constipation, and
When perillaldehyde component content is in 46-49.2%, carypohyllene component content in 14.5-22%, perillene or perilla ketone 0-4.1%,
Wherein, when perillaldehyde and total content both carypohyllene is in the range of 62-68%, perillaldehyde type perilla leaf oil shows extremely strong
Promotion Constipation, have pole significant difference (p compared with control group<0.01).
Summarize：
1st, perillaldehyde type perilla leaf oil, perilla ketone type perilla leaf oil have antipyretic response；
2nd, perilla ketone type perilla leaf oil has toxicity, and perillaldehyde type does not have toxicity；
3rd, research discovery is carried out to perillaldehyde type perilla leaf oil, the perillaldehyde type perilla leaf oil that the present invention limits, which has, to be promoted
Small bowel peristalsis, antipyretic, anti-inflammatory, antibacterial effect, there may be relation with perillaldehyde, the proportioning of carypohyllene and weight.
Claims (10)
1. a kind of new perilla leaf oil, it is characterised in that the percentage by weight of the active ingredient component wherein contained is as follows：Purple perilla
Aldehyde 29-70%, carypohyllene 2-27%, perillene or perilla ketone 0-5%, wherein, total content of both perillaldehyde and carypohyllene
For 40-85%.
2. perilla leaf oil according to claim 1, it is characterised in that the weight percent of the active ingredient component wherein contained
Than as follows：Perillaldehyde 35-70%, carypohyllene 7-27%, perillene or perilla ketone 0-5%, wherein, both perillaldehyde and carypohyllene
Total content be 45-85%.
3. perilla leaf oil according to claim 1, it is characterised in that the weight percent of the active ingredient component wherein contained
Than as follows：Perillaldehyde 40-62%, carypohyllene 10-27%, perillene or perilla ketone 0-4.1%, wherein, perillaldehyde and carypohyllene
The total content of the two is 56-85%.
4. perilla leaf oil according to claim 1, it is characterised in that the weight percent of the active ingredient component wherein contained
Than as follows：Perillaldehyde 40-55%, carypohyllene 14-22%, perillene or perilla ketone 0-4.1%, wherein, perillaldehyde and carypohyllene
The total content of the two is 60-70%.
5. perilla leaf oil according to claim 1, it is characterised in that the weight percent of the active ingredient component wherein contained
Than as follows：Perillaldehyde 40-53%, carypohyllene 14-22%, perillene or perilla ketone 0-4.1%, wherein, perillaldehyde and carypohyllene
The total content of the two is 60-70%.
6. perilla leaf oil according to claim 1, it is characterised in that the weight percent of the active ingredient component wherein contained
Than as follows：Perillaldehyde 46-49.2%, carypohyllene 14.5-22%, perillene or perilla ketone 0-4.1%, wherein, perillaldehyde and stone
Total content of both bamboo alkene is 62-68%.
7. the preparation method of the perilla leaf oil described in claim any one of 1-6, this method comprise the following steps：
By perilla leaf steam distillation, steam pressure is maintained at 0.1MPa, the timing since oil dripping, distills 3-5 hours, temperature
100-120 DEG C, distillate is collected after steam condensation, the dregs of a decoction discard, and distillate stands more than 20 minutes, obtains water layer, volatile oil
Layer and emulsion layer, isolate volatilization oil reservoir, emulsion layer carries out secondary water steam in addition, the present invention also creatively collects water layer
Distillation, distillation time are 30 minutes separation volatilization oil reservoirs, emulsion layer and the volatile oil obtained respectively with first time steam distillation
Layer, emulsion layer mixing, discard water layer, emulsion layer are stood, and emulsion layer stands more than 12h, merge volatilization oil reservoir and produce perilla leaf
Oil.
8. the perilla leaf oil described in claim any one of 1-6 is preparing antibacterial, anti-inflammatory, is promoting small bowel peristalsis, antipyretic medicine
In application.
9. application according to claim 8, it is characterised in that the medicine is perilla herb oil list product or contains perilla leaf oil
Compound.
10. the pharmaceutical preparation containing the perilla leaf oil described in claim any one of 1-6, it is characterised in that add medicine if necessary
Acceptable carrier on.
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| CN201610840075X | 2016-09-22 | ||
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112057532A (en) * | 2020-09-10 | 2020-12-11 | 王红军 | Nasal drops for treating upper respiratory tract inflammation and preparation method thereof |
| CN113125604A (en) * | 2021-04-16 | 2021-07-16 | 上海和黄药业有限公司 | Method for determining contents of perillaldehyde, perillaketone and perillene in perilla leaf oil |
Citations (1)
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| CN106244330A (en) * | 2016-08-26 | 2016-12-21 | 云南养瑞科技集团有限公司 | The preparation method of a kind of Pericarpium Citri Reticulatae quintessence oil and the application in Medicated cigarette thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106244330A (en) * | 2016-08-26 | 2016-12-21 | 云南养瑞科技集团有限公司 | The preparation method of a kind of Pericarpium Citri Reticulatae quintessence oil and the application in Medicated cigarette thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112057532A (en) * | 2020-09-10 | 2020-12-11 | 王红军 | Nasal drops for treating upper respiratory tract inflammation and preparation method thereof |
| CN113125604A (en) * | 2021-04-16 | 2021-07-16 | 上海和黄药业有限公司 | Method for determining contents of perillaldehyde, perillaketone and perillene in perilla leaf oil |
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